An assessment of the risk of neoplasia in long-term ileal reservoirs using the DMH rodent model.
This study was undertaken to determine if the construction of an ileal reservoir induces mucosal changes that can potentiate the effect of a chemical carcinogen (1,2-dimethylhydrazine) on ileal mucosa. Animals were divided into three groups: 1) sham operation (n = 19), 2) total colectomy with ileorectal anastomosis (n = 20), 3) total colectomy with an ileal reservoir made of terminal ileum sutured to the rectum (n = 20). An adaptation period of 12 weeks was allowed to promote fecal stasis and the histologic changes before exposure to weekly subcutaneous injections of DMH (25 mg/kg) for 16 weeks. Sodium butyrate was added to the diet as a tumor promotor. All animals were sacrificed one month later. Fecal stasis, along with enlargement, occurred in all the reservoirs (mean dimensions, 74 X 58 X 43 mm). Their mean volume was 88 +/- 14 ml. The histologic changes in the ileal reservoirs were: chronic inflammation (14/20), villous atrophy (14/20), and atrophy of the glands (8/20). In group 3, five carcinomas were seen. There were three in the duodenum and two in the reservoirs. In contrast, 21 carcinomas were detected in the control groups. There were 17 in the colon, 3 in the jejunum, and 1 in the ileum. No significant difference in the number of carcinomas was seen in the ileum with and without reservoir. Although it is possible to induce carcinomas in ileal reservoirs, the incidence remained significantly less than in the colon. In conclusion, the histologic changes induced by the construction of an ileal reservoir do not increase the risk of malignant transformation in the DMH model for intestinal carcinogenesis.
Heppell
J
J
Department of Surgery and Pathology, Hôtel-Dieu de Montréal, Université de Montréal, Québec, Canada.
De Zubiria
M
M
Brais
M F
MF
Durh
M A
MA
Carioto
S
S
Boivin
Y
Y
Potvin
C
C
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced; D004127:Dimethylhydrazines / Q000633:toxicity; D007078:Ileal Neoplasms / Q000139:chemically induced*; D007081:Ileostomy / Q000009:adverse effects*; D007082:Ileum / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; D004127:Dimethylhydrazines; D019813:1,2-Dimethylhydrazine